(−)-Vibo-quercitol ((1R,2R,4S,5R)-cyclohexane-1,2,3,4,5-pentol) is a compound having the following chemical structure discovered from plants of the Asclepiadaceae family.

(−)-Vibo-quercitol has been shown to have a potent hypoglycemic action. Deoxyinosamine and deoxyinosamidine [sic], which can be obtained by amination of (−)-vibo-quercitol, are also compounds that can serve as synthesis intermediates for various pharmaceuticals and agricultural chemicals (Patent References 1 and 2).
The industrial utility of (−)-vibo-quercitol has also become apparent in recent years. For example, Patent Reference 3 describes (−)-vibo-quercitol as being useful as an additive for preventing freezing of the coolant in a fuel cell. When used for this purpose, (−)-vibo-quercitol is not oxidized even after long-term use and maintains suitable properties.
Patent Reference 4 focuses on the fact that (−)-vibo-quercitol can absorb and emit a large amount of latent heat during the process of dissolution and solidification, and discloses the application of this compound to a heat-storage material for the heat storage of solar heat and for efficiently utilizing inexpensive nighttime power.
A clear need therefore exists to produce (−)-vibo-quercitol efficiently by a simple process. When (−)-vibo-quercitol is utilized as an active ingredient of a pharmaceutical, the bulk form of the compound should be as pure as possible and should not include any unidentified impurities. The production process should therefore also be as simple as possible, and the production history should be easily tracked. The production cost can also affect the feasibility of the technology when (−)-vibo-quercitol is used for industrial purposes such as those mentioned above.
Classically, (−)-vibo-quercitol is extracted from plants of the Asclepiadaceae family. However, a method of culturing microorganisms of the genus Agrobacterium or genus Salmonella using myo-inositol as a substrate, causing (−)-vibo-quercitol to be produced together with (+)-proto-quercitol and (+)-epi-quercitol in the culture broth, and isolating (−)-vibo-quercitol from the culture broth has been proposed in recent years as a more efficient method. A method of bringing cells of these microorganisms of the genus Agrobacterium or genus Salmonella into contact with myo-inositol, causing (−)-vibo-quercitol to be produced together with (+)-proto-quercitol and (+)-epi-quercitol in the reaction solution, and isolating (−)-vibo-quercitol from the reaction solution has also been proposed (Patent References 1 and 2).
However, no enzyme that converts myo-inositol into (−)-vibo-quercitol in this method has been isolated, and it is not even clear whether the reaction is due to one enzyme or whether two or more enzymes are involved. Therefore, since culturing microorganism with myo-inositol as a substrate or at least utilizing cells obtained from a culture of these microorganisms is essential in this method, the process remains complex and is associated with the risk of contamination by unknown impurities.
Patent Reference 5 also proposes a method for culturing Enterobacter sp. AB10114 (FERM P-19319), a microorganism of the genus Enterobacter, using myo-inositol as a substrate, causing (−)-vibo-quercitol to be produced in the culture broth, and isolating (−)-vibo-quercitol from the culture broth. (−)-Vibo-quercitol is obtained at a yield of about 25% from myo-inositol in this method (see Example 1). In this method again, however, no enzyme that converts myo-inositol into (−)-vibo-quercitol has been isolated. Therefore, since culturing microorganisms with myo-inositol as a substrate is essential in this method as well, the process again is complex and associated with a risk of contamination by unknown impurities. In addition, even this method cannot avoid a microbial fermentation process requiring time and effort to obtain the target (−)-vibo-quercitol.
Furthermore, Patent Reference 6 discloses a method for converting (−)-vibo-quercitol into 2-deoxy-scyllo-inosose by contact with the Enterobacter sp. AB10114 (FERM P-19319) used in the method of the abovementioned Patent Reference 5. In brief, Enterobacter sp. AB10114 (FERM P-19319) is said to convert (−)-vibo-quercitol into 2-deoxy-scyllo-inosose at a yield of 80% (see Example 1). Although the details are not clear since no enzyme is isolated either in Patent Reference 6, it is reasonable to assume that, even if this reaction is catalyzed by a single enzyme, the activity of at least that enzyme is predominant in the direction converting (−)-vibo-quercitol into 2-deoxy-scyllo-inosose, and it is difficult for a substantially reverse reaction to progress.
On the other hand, the inventors do not know of any enzyme previously reported to convert 2-deoxy-scyllo-inosose directly into (−)-vibo-quercitol as shown in the following reaction scheme.
